Structure and function study of Ca2+ channel Orai1 in esophageal cancer
Orai1, a plasma membrane store operated Ca2+ entry (SOCE) channel may act as an oncogene that contributes to the progression of esophageal cancer through regulation of intracellular Ca2+ oscillations. In tumors removed from patients with esophageal squamous cell carcinoma (ESCC), we found elevated expression of Orai1 and the high expression level appeared to associate with poor survival rate in patients with this disease. We also showed that inhibition of Orai1 could prevent tumor growth in xenograft ESCC mouse model. Currently, we are studying the molecular mechanisms underlying the hyperactivity of Ca2+ oscillations resulting from elevated Orai1-SOCE.
The long-term goal is to reveal the disease specific regulatory components of Orai1-Ca2+ signaling pathways. Another goal is to evaluate whether SOCE machinery genes can serve as novel biomarker for early detection and prognosis in Barrett’s esophageal, esophageal adenocarcinoma and squamous cell carcinoma. The study will provide proof-of-principle data on targeting this pathway as a potential treatment for esophageal cancers.
Dysregulated Ca2+ signaling in diabetic cardiovascular complications
Diabetic cardiovascular complications are complex diseases influenced by numerous genetic and environmental factors. We are interested to study the disrupted Ca2+ homeostasis in type 2 diabetes mellitus (T2DM) patients with atrial fibrillation (AFb) or other cardiovascular complications. Using multidiscipline approach, including differential gene screening, novel dual-targeting CRISPR/cas9 KO technique and structure biochemistry, we aim to reveal the mechanism underlying the arrhythmogenic role of autoantibodies.
The long-term goal is to search for novel biomarkers to assess the environmental risk factors for AFb in T2DM and shed light to possible clinical trials for diabetic patients with high risk of AFb and/or cardiac conductance disorders targeting downstream Ca2+ signaling pathway.
Nanoparticle based imaging and treatment of esophageal cancer
Despite of its extremely aggressive nature and poor survival rate, advanced esophageal cancer remains to be one of the least studied cancers. Nanoparticle based drug delivery can prolong drug half-time, improve solubility of hydrophobic drugs and reduce potential immunogenicity, which can be a promising therapy. Through collaboration with some nanotechnology experts at The Ohio State University and UTA, we are interested to develop nanoplatforms for simultaneous imaging and treatment of esophageal cancer, such as using a biocompatible, fluorescent polypeptide based nanoplatform or copper-cysteamine nanoparticles for a microwave induced photodynamic therapy.
Our goal is to develop these nanoparticles with enhanced tumor targeting and penetration as a safe and effective new cancer therapy.
